A large fraction of human breast tumors contain estrogen receptors and, thus, have the ability to concentrate estrogenic substances. In principle, one should be able to utilize this selective uptake mechanism to concentrate a gamma-emitting radiopharmaceutical whose distribution could be monitored by gamma-imaging techniques. Such a procedure would provide a unique, non-invasive diagnostic tool for localizing breast tumors and metastases and determining their receptor content. This project is concerned with the synthesis and evaluation of such receptor-based, selective breast tumor localizing agents. Halogenated derivatives (fluorine-18, bromine-77 and iodine-123) of various steroidal and non-steroidal estrogens will be prepared. The halogen will be placed at a position consistent with high chemical and metabolic stability and high receptor binding affinity, and the overall structure of the molecule will be designed to maximize its binding selectivity. This will be done by adjusting its structure to optimize its "binding selectivity index" (BSI), which is defined as the ratio of its binding affinity to the estrogen receptor to its binding affinity to non-specific binding sites. These compounds will be evaluated in in vitro binding assays to determine their affinity for the estrogen receptor. Those with high BSI values will be prepared in radiolabeled form and their tissue distribution will be determined in immature rats and in mature rats bearing DMBA-induced mammary tumors. Tissue to blood ratios will be determined at various times, and receptor-mediated uptake will be determined by competition with unlabeled estradiol. Rats injected with the compounds prepared in gamma-emitting form will be imaged under a gamma camera.